Method and apparatus for treating cardiac arrythmia

ABSTRACT

An implantable system for the cardioversion of the heart of a patient in need of such treatment comprises a plurality of primary electrodes, a power supply, and a control circuit. Preferably, at least one auxiliary electrode is also included. The plurality of primary electrodes are configured for delivering a cardiversion pulse along a predetermined current pathway in a first portion of the heart, the current pathway defining a weak field area in a second portion of the heart.

RELATED APPLICATIONS

This application is a continuation-in-part of application Ser. No.09/039,143, filed Mar. 13, 1998, now issued as U.S. Pat. No. 5,978,705which is a continuation-in-part of application Ser. No. 08/818,261,filed Mar. 14, 1997 now abandon, the disclosures of both of which isincorporated by reference herein in their entirety.

FIELD OF THE INVENTION

The present invention relates to methods and an implantable apparatusfor treating cardiac arrhythmia, particularly ventricular fibrillation.

BACKGROUND OF THE INVENTION

One object in developing implantable defibrillation apparatus has beento lower the shock strength produced by that apparatus so that the sizeof the shock capacitor, and hence the size of the implantable apparatusitself, can be reduced. Several approaches to achieving this goal havebeen taken. U.S. Pat. No. 4,780,145 to Tacker et al. discusses theproblem with single-pulse defibrillation systems in that the currentdensity between the electrodes is not uniform throughout the ventricles.Tacker describes a sequential-pulse, multiple current pathwaydefibrillation method in which two defibrillation pulses are deliveredalong different current pathways.

U.S. Pat. No. 5,536,764 to Adams et al. and U.S. Pat. No. 5,344,430 toBerg et al. both describe implantable defibrillation systems employingtwo or more successive pulses, but again all pulses are defibrillationpulses. Similarly, U.S. Pat. No. 5,324,309 to Kallok describessuccessive defibrillation pulses that overlap in time. Adams et al.point out that, after four separate defibrillation attempts, therapy isterminated because conversion thresholds increase with time in afibrillation episode, and that patients are likely to suffer braindamage after prolonged fibrillation. Hence, it is extremely desirable toincrease the likelihood of successful defibrillation on an earlyattempt: a goal not always consonant with that of decreasing shockstrength.

Other implantable defibrillators employ pacing, or pretreatment, pulses.U.S. Pat. No. 5,366,485 to Kroll et al. and U.S. Pat. No. 4,559,946 toMower et al. both describe defibrillation apparatus in which pacing orpretreatment pulses are delivered through the same electrodes as thedefibrillation pulse. U.S. Pat. No. 4,693,253 to Adams and U.S. Pat. No.5,431,682 to Hedberg both describe defibrillation apparatus in whichpacing pulses are delivered after defibrillation. U.S. Pat. No.5,282,836 to Kreyenhagen et al. describes an atrial defibrillatorwherein pacing pulses are delivered through a pacing electrode prior todefibrillation pulses being delivered through a separate set ofdefibrillationelectrodes.

U.S. Pat. No. 5,489,293 to Pless et al. describes an apparatus fortreating cardiac tachyarrhythmia which uses a lower voltagedefibrillation apparatus by providing a rapid sequence of defibrillationshocks synchronized with sensed sequential cardiac or electrogram eventsor features during an arrhythmia.

U.S. Pat. No. 5,464,429 to Hedberg et al. describes an apparatus inwhich a stimulation pulse is delivered through an electrode thatordinarily serves as a pacing electrode, with the stimulation pulsebeing delivered prior to a defibrillation pulse (the latter beingdelivered through separate defibrillation electrodes). The stimulationpulse is of a magnitude greater than that of a pacing pulse, but lessthan that of a defibrillation pulse, and is said to produce a refractoryarea around the stimulation electrode. However, the stimulation pulse isdelivered via an electrode that also serves as a pacing electrode,rather than an electrode specifically positioned in a weak field area ofthe defibrillation electrodes. The use of a stimulation pulse of areverse polarity to the first phase of a biphasic defibrillationpulse isnot disclosed.

U.S. Pat. No. 5,282,837 to Adams et al. (InControl, Inc.)(see alsoDivisional application Ser. No. 5,282,837) describes, in FIG. 1 andaccompanying text, an atrial defibrillator and method in which a lead 36is inserted into the coronary sinus so that a first tip electrode 42 iswithin the coronary sinus adjacent the left ventricle, a second ringelectrode 44 is within the coronary sinus beneath the left atrium, andthe third electrode 46 within the right atrium or superior vena cava.The first electrode serves as a sensing electrode, the second electrode(still in the coronary sinus) serves as both a sensing anddefibrillating electrode, and the third electrode serves as a sensingand defibrillating electrode (see Col. 5 line 57 to Col. 6 line 12).

U.S. Pat. No. 5,433,729 to Adams et al. (corresponds to PCT WO92/18198)is a CIP of Adams '837. Adams '729 describes, in FIG. 9 and accompanyingtext, a lead system 250 configured in accordance with that describedabove. A first (right ventricle) lead 252 includes an elongate largesurface area electrode 256, a distal or tip sense electrode 258, and aring or proximal sense electrode 260. Sense electrodes 258, 260 arepositioned in and in contact with the wall of the right ventricle, andelongate electrode 256 is in the right atrium. A second (coronary sinus)lead 254 includes a tip, or distal sense electrode 264, a ring orproximal sense electrode 266, and a second elongate, large surface areaelectrode 262. Distal and proximal sense electrodes 264, 266 are bothadjacent the left ventricle within the great vein, and elongateelectrode 262 is within the coronary sinus beneath the left atrium. Theright ventricle sense electrodes 258, 260 are coupled to inputs 50 a, 50b of first sense amplifier 50; the great vein sense electrodes 264, 266are coupled to inputs 52 a, 52 b of second sense amplifer 52. This is toprovide sensing of the right ventricle and the left ventricle, and thenon-coincident sensing of the depolarization activation waves. forsynchronizing delivery of energy to the atria (see column 15 line 34 tocolumn 16 line 54; column 5 lines 62-64).

U.S. Pat. No. 5,014,696 to Mehra (Medtronic Inc.) describes anendocardial defibrillation electrode system in which a coronary sinuselectrode extending from an area adjacent the opening of the coronarysinus and terminating in the great vein is used in combination withsubcutaneous plate electrodes and with right ventricular electrodes. Thecoronary sinus electrode 78 encircles the left ventricle cavity 86 (Col.5 lines 50-51; FIG. 5B). It is stated “it is important not to extend theelectrode 78 downward through the great vein 80 toward the apex 79 ofthe heart” (col. 5 lines 28-30). U.S. Pat. No. 5,165,403 to Mehra(Medtronic, Inc.) describes an atrial defibrillation electrode 112 thatis located “within the coronary sinus and the great cardiac vein.”

U.S. Pat. No. 5,099,838 to Bardy (filed Dec. 15, 1988; Medtronic, Inc.)describes a defibrillation electrode in the great vein that is used incombination with subcutaneous plate electrodes and with rightventricular electrodes (col. 1 line 65 to col. 2 line 2). With respectto the great vein electrode, it is stated at column 5, lines 20-33therein: “When so mounted, the elongate defibrillation electrode 78extends from a point adjacent the opening of the coronary sinus 74 andinto the great vein 80. This provides a large surface areadefibrillation electrode which is generally well spaced from theventricular defibrillation electrode 74 and provides good currentdistribution in the area of the left ventricle 77. It is desireable toextend the electrode 78 around the heart as far as possible. However, itis important not to extend the electrode 78 downward through the greatvein 80 toward the apex 79 of the heart, as this will bring the coronarysinus and right ventricular electrodes into close proximity to oneanother, interfering with proper current distribution. U.S. Pat. No.5,193,535 to Bardy (filed Aug. 27, 1991) also describes a great veinelectrode. At column 7, lines 31-35, it is stated: “The coronary sinuslead is provided with an elongated electrode located in the coronarysinus and great vein region at 112, extending around the heart untilapproximately the point at which the great vein turns downward towardthe apex of the heart.”

U.S. Pat. No. 5,431,683 to Bowald et al. (Siemens) describes aventricular defibrillation electrode system in which on electrode isplaced through the coronary sinus into a peripheral vein of the heart.The term “peripheral vein” is defined therein as to encompass “thevenous side of the coronary vessels running between the base and theapex of the heart. The [sic] include the middle and small cardiac veins,and the portion of the great cardiac vein which runs between the baseand apex of the heart.

The definition of “peripheral veins” used herein, therefore, excludesthat portion of the great cardiac vein which runs along the base planeof the heart, which has been used [as] a site for electrode placement inprior art electrode systems.” The electrodes are in the shape of a helixto apply pressure against the inner wall (col. 4, lines 14-17), withblood being able to flow unobstructed through the interior of the helix(column 4, lines 46-48)(See also U.S. Pat. No. 5,423,865 to Bowald).Such stent-type electrodes can be difficult to adjust or remove. Only asimple shock pattern is described in Bowald, and efficacious electrodeconfigurations and shock patterns are neither suggested nor disclosed.

U.S. Pat. No. 5,690,686 to Min et al. (Medtronic Inc.) describes anatrial defibrillation method in which a coronary sinus/great veinelectrode is coupled to a right atrial/superior vena cava electrode anda subcutaneous electrode in the form of the housing of an implantabledefibrillator. The device is stated to be preferably practiced as acombined atrial/ventricular defibrillator (col. 2, lines 26-35).

In view of the foregoing, a first object of the invention is to providean implantable system for treating cardiac arrythmia that does notrequire invasion of the chest cavity for the placement of epicardialelectrodes.

A second object of the invention is to provide an implantablecardioversion system wherein the probability of successful cardioversionon administration of the first cardioversionpulse is enhanced,particularly in the case of ventricularfibrillation.

A third object of the invention is to provide an implantable system fortreating cardiac arrythmia that can enable reduction of cardioversion,and particularly defibrillation, shock strength.

SUMMARY OF THE INVENTION

A first aspect of the present invention is an implantable system for thedefibrillation or cardioversion of a patient's heart, or theadministration of antitachycardia pacing to a patient's heart. Thesystem comprises a plurality of primary electrodes, a power supply, anda control circuit. The plurality of primary electrodes are configuredfor delivering a defibrillation pulse, cardioversion pulse, orantitachycardia pacing along a predetermined current pathway in a firstportion of the heart, with a first one of the primary electrodesconfigured for positioning through the coronary sinus and within a veinon the surface of the left ventricle of the heart. The control circuitis operatively associated with the power supply and the primaryelectrodes, and the control circuit is configured for delivering adefibrillation pulse through the primary electrodes.

A second aspect of the present invention is an implantable system forthe defibrillation or cardioversion of the heart of a patient in need ofsuch treatment. The system comprises a plurality of primary electrodes,at least one auxiliary electrode, a power supply, and a control circuit.The plurality of primary electrodes are configured for delivering adefibrillation pulse along a predetermined current pathway in a firstportion of the heart, the current pathway defining a weak field area ina second portion of the heart. The weak field area is the portion of theheart where the defibrillation shock field intensity is at or near aminimum. At least one auxiliary electrode is configured for deliveringan auxiliary pulse to the weak field area. The control circuit isoperatively associated with the primary electrodes, the auxiliaryelectrode, and the power supply, with the control circuit configured fordelivering a cardioversion sequence comprising an auxiliary pulsesufficient to alter transmembrane potential in the weak field areathrough the auxiliary electrode, followed by a defibrillation pulsethrough the primary electrodes delivered while the electrophysiologicaleffects imparted by the auxiliary pulse in the weak field area arepresent.

One preferred embodiment of the foregoing apparatus is an implantablesystem for the defibrillation of the ventricles of the heart of apatient in need of such treatment. The system comprises a plurality ofprimary electrodes, at least one auxiliary electrode, a power supply,and a control circuit. The plurality of primary electrodes areconfigured for delivering a defibrillation pulse along a predeterminedcurrent pathway in a first portion of the heart, the current pathwaydefining a weak field area in a second portion of the heart. At leastone auxiliary electrode is configured for delivering an auxiliary pulseto the weak field area, with the at least one auxiliary electrodeconfigured for positioning through the coronary sinus and in a vein onthe surface of the left ventricle of the heart. The control circuit isoperatively associated with the primary electrodes, the at least oneauxiliary electrode, and the power supply, the control circuitconfigured for delivering a cardioversion sequence comprising amonophasic auxiliary pulse through the auxiliary electrode, followed bya biphasic defibrillation pulse through the primary electrodes, with thedefibrillation pulse delivered within 20 milliseconds after theauxiliary pulse, and with the first phase of the defibrillationpulse inopposite polarity to the auxiliary pulse.

Primary electrodes and auxiliary electrodes may be carried by one ormore transvenous leads, and the implantable defibrillator housing maycarry an electrode on the outer surface thereof.

In alternate embodiments of the invention, the order of thecardioversion sequence may be reversed, so that the sequence comprises adefibrillation pulse through the primary electrodes, followed by anauxiliary pulse sufficient to alter transmembrane potential in the weakfield area through the auxiliary electrode while theelectrophysiological effects imparted by the primary pulse in the weakfield area are present. Parameters for the two shocks (time intervals,shock strength and polarities) are otherwise the same. However, when theauxiliary pulse is delivered after the primary, or defibrillation,pulse, the auxiliary pulse is preferably a biphasic pulse (in this case,the primary pulse may optionally be monophasic).

A still further object of the present invention is an electrode leaduseful for the cardioversion or defibrillation of a patient's heart. Thelead comprises an elongate transveneous electrode lead having a distalend portion, with the lead configured for positioning the distal endportion within the right atrial appendage or the right ventricularoutflow track, and a primary electrode connected to the electrode leadand positioned on the distal end portion thereof.

The foregoing and other objects and aspects of the present invention aredescribed in greater detail in the drawings herein and the specificationset forth below.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a preferred set of electrode placements in anapparatus for carrying out the present invention;

FIG. 2 schematically illustrates the control circuitry employed in anapparatus of the present invention;

FIG. 3 illustrates a waveform that may be used to carry out the presentinvention;

FIG. 4 illustrates a preferred waveform that may be used to carry outthe present invention;

FIG. 5 illustrates an alternate set of cardiac electrode placements inan apparatus for carrying out the present invention;

FIGS. 6A and 6B illustrates endocardial electrodes that may be used tocarry out the apparatus illustrated in FIG. 5;

FIG. 7 schematically illustrates how an apparatus of the presentinvention is modified to control the therapy delivered;

FIG. 8 schematically illustrates the thirteen treatment procedures,including control, used in Example 1 below;

FIG. 9 provides histograms of the mean delivered energy atdefibrillation threshold for pulsing schema utilizing auxiliary shocksaccording to FIG. 8;

FIG. 10 is similar to FIG. 9 above, except delivered energy is expressedas leading edge voltage rather than in Joules;

FIG. 11 schematically illustrates transvenous electrode placement in theclosed chest dog model described in Example 2 below;

FIG. 12 schematically illustrates seven treatment protocols used inExample 2 below;

FIG. 13a illustrates a set of waveforms and electrode configurationsthat may be used to practice the present invention;

FIG. 13b illustrates a set of waveforms and electrode configurationsthat may be used to practice the present invention;

FIG. 13c illustrates a set of waveforms and electrode configurationsthat may be used to practice the present invention; and

FIG. 13d illustrates a set of waveforms and electrode configurationsthat may be used to practice the present invention.

DETAILED DESCRIPTION OF THE INVENTION

The present invention may be used to treat all forms of cardiactachyarrythmias, including ventricular fibrillation, with defibrillation(including cardioversion) shocks or pulses, including antitachycardiapacing. The treatment of polymorphic ventricular tachycardia andventricular fibrillation are particularly preferred.

The antitachycardia pacing may be delivered from the primary electrodeplaced through the coronary sinus ostium and within a vein on thesurface of the left ventricle alone, or may be coupled to or yolked toan additional electrode, such as an electrode positioned in the rightventricle. An independent right ventricle may be provided as analternate source of antitachycardia pacing, based upon the origin of thetrigger and cross channel syntactic patterns. Antitachycardia pacing maybe delivered from the right ventricle and then the left ventricleelectrode, or may be delivered from the left ventricle and then theright ventricle electrode.

Anatomically, the heart includes a fibrous skeleton, valves, the trunksof the aorta, the pulmonary artery, and the muscle masses of the cardiacchambers (i.e., right and left atria and right and left ventricles). Theschematically illustrated portions of the heart 30 illustrated in FIG. 1includes the right ventricle “RV” 32, the left ventricle “LV” 34, theright atrium “RA” 36, the left atrium “LA” 38, the superior vena cava48, the coronary sinus “CS” 42, the great cardiac vein 44, the leftpulmonary artery 45, and the coronary sinus ostium or “os” 40.

The driving force for the flow of blood in the heart comes from theactive contraction of the cardiac muscle. This contraction can bedetected as an electrical signal. The cardiac contraction is triggeredby electrical impulses traveling in a wave propagation pattern whichbegins at the cells of the SA node and the surrounding atrial myocardialfibers, and then traveling into the atria and subsequently passingthrough the AV node and, after a slight delay, into the ventricles.

The beginning of a cardiac cycle is initiated by a P wave, which isnormally a small positive wave in the body surface electrocardiogram.The P wave induces depolarization of the atria of the heart. The P waveis followed by a cardiac cycle portion which is substantially constantwith a time constant on the order of 120 milliseconds (“ms”).

Various embodiments of the present invention can be illustrated withreference to FIG. 1. The defibrillator 10 of FIG. 1 includes animplantable housing 13 that contains a hermetically sealed electroniccircuit 15 (see FIG. 2). The housing includes an electrode comprising anactive external portion 16 of the housing, with the housing 13preferably implanted in the left or right thoracic region of the patient(e.g., subcutaneously or submuscularly, in the left or right pectoralregion, or subcutaneously or submuscularly in the left or right(preferably left) abdominal region; the left pectoral region is mostpreferred) in accordance with known techniques as described in G. Bardy,U.S. Pat. No. 5,292,338.

The system includes a first catheter 20 and a second catheter 21, bothof which are insertable into the heart (typically through the superioror inferior vena cava) without the need for surgical incision into theheart. The term “catheter” as used herein includes “stylet” and is alsoused interchangeably with the term “lead”. Each of the catheters 20, 21contains electrode leads 20 a, 20 b, 21 a, respectively.

As illustrated in FIG. 1, the system includes an electrode A; 50 thatresides in the superior vena cava or innominate vein, an electrode B; 51positioned in the right ventricle, and an electrode C; 52 positionedwithin a vein on the postero lateral surface of the left ventricle(e.g., in the apical third of the posterior cardiac vein or the apicalhalf of the great cardiac vein). The active external portion of thehousing 16 serves as a fourth electrode D. Designations “A” through “D”herein refer to electrodes in the aforesaid positions.

Electrode C may be a hollow electrode to allow the flow of blood throughthe electrode (e.g., a stent-type electrode that engages the vesselwall) when positioned in the vein, or may be a solid electrodeconfigured (that is, of a shape and size) to allow the flow of bloodaround the electrode when positioned within the vein. A solid electrodeis preferred. Electrode C may be positioned entirely within a vein onthe postero-lateral surface of the left ventricle, or may also extendinto the coronary sinus (as in the case of an elongate electrode).

The position of electrode C may be achieved by first engaging thecoronary sinus with a guiding catheter through which a conventionalguidewire is passed. The tip of the torqueable guidewire is advancedunder fluoroscopic guidance to the desired location. The lead 21 onwhich electrode C is mounted passes over the guidewire to the properlocation. The guidewire is withdrawn and electrode C is incorporatedinto the lead system. Such an electrode is considered a solid-typeelectrode herein.

FIG. 2 illustrates one example of an implantable housing 13 containingan electronic circuit 15, which includes one or more amplifiers (notshown) for amplifying sensed cardiac signals. The amplified signals areanalyzed by an detector 70 which determines if ventricular fibrillation(or other arrythmia, depending on the specific treatment for which thedevice is configured) is present. The detector 70 may be one of severalknown to those skilled in the art. Although, as illustrated, a sensingsignal is provided by the electrode A 50, it will be appreciated bythose of skill in the art that the sensing electrode may also be aplurality of sensing electrodes with a plurality of signals, such asbipolar configurations, and may also be electrodes that are positionedin alternate cardiac areas as is known in the art, such as for example,the CS. In this situation, the input line to the detector may be aplurality of lines which if providing only sensing will provide an inputto the detector.

The defibrillationelectrodes may alternately be configured to sensecardiac cycles, or may have smaller sensing electrodes placed adjacentthereto and thereby provide input to the electronics package as well asprovide a predetermined stimulation shock output to predeterminedcardiac areas as directed by the controller.

The electronic circuit 15 also includes a cardiac cycle monitor(“synchronization monitor 72”) for providing synchronization informationto the controller 74. As discussed below, the synchronization istypically provided by sensing cardiac activity in the RV, but may alsoinclude other sensing electrodes which can be combined with thedefibrillation electrodes or employed separately to provide additionalassurance that defibrillation shock pulses are not delivered duringsensitive portions of the cardiac cycle so as to reduce the possibilityof inducing ventricular fibrillation.

Numerous configurations of capacitor and control circuitry may beemployed. The power supply may include a single capacitor, and thecontrol circuit may be configured so that both the auxiliary pulse andthe defibrillation pulse are generated by the discharge of the singlecapacitor. The power supply may include a first and second capacitor,with the control circuit configured so that the auxiliary pulse isgenerated by the discharge of the first capacitor and the defibrillationpulse is generated by the discharge of the second capacitor. In stillanother embodiment, the power supply includes a first and secondcapacitor, and the control circuit may be configured so that theauxiliary pulse is generated by the discharge (simultaneous orsequential) of both the first and second capacitors, and thedefibrillation pulse likewise generated by the discharge of the firstand second capacitors. The controller's power supply may include a 20 to400 microfared capacitor.

One defibrillation waveform that may be used to carry out the presentinvention is illustrated in FIG. 3, which shows a schematic illustrationof a biphasic truncated exponential waveform. While a variety ofdifferent waveforms can be used, as discussed herein, surprisingly goodresults are achieved when an auxiliary pulse is delivered prior to theprimary, or defibrillation, pulse, with the auxiliary pulse beingdelivered along a different current pathway. A particularly surprisingfinding was that better results can be achieved when the auxiliary pulseis of an opposite polarity than the first phase of the defibrillationpulse. Such a biphasic truncated exponential waveform primary pulse witha monophasic auxiliary pre-pulse is illustratedin FIG. 4. The foregoingwaveforms can be modified in ways that will be apparent to those skilledin the art (e.g., a chopped waveform can be delivered; the waveform canbe time-based or fixed tilt; etc).

The auxiliary pulse may be from 0.5 or 1 to 5 or 10 milliseconds induration, with a 2 millisecond pulse currently preferred. The timeinterval from the end of the auxiliary pulse to the leading edge of theprimary pulse may be from 1 or 2 milliseconds to 10, 15 or 20milliseconds, with a delay of about 5 milliseconds currently preferred.

The optimal auxiliary-to-primary interval may differ depending on thetype of rhythm or condition of the myocardial tissue at the time thetherapy is applied. Therefore, the control circuitry may also beconfigured to sense a characteristic of the cardiac rhythm (e.g., anactivation interval or a dynamical pattern of consecutive activationintervals) and then select an optimum auxiliary-to-primary shock timeinterval (e.g., from a look up table stored in a microprocessormemory).

The percent tilt of the primary pulse and the auxiliary pulse may eachbe from 10, 20 or 30 percent up to 50 or 60 percent. Percenttilt=(Vo−Vf×100)/Vo, where Vo is the initial voltage and Vf is the finalvoltage of the pulse. Vf refers to the final voltage of the final phaseof the shock where the shock sequence has multiple phases.

In general, the control circuit is configured so that the auxiliarypulse is not more than 40% or 50% of the peak current and not more than20% or 30% of the delivered energy (in Joules) of the defibrillationpulse. In a preferred embodiment, the trailing edge voltage of theauxiliary pulse is equal (±10 Volts) to the leading edge voltage of thedefibrillation pulse. Particular voltage, current, and energy outputswill depend upon factors such as the condition of the tissue and theparticular disorder being treated. In general, the auxiliary pulse mayhave a peak voltage of from 20 or 30 volts to 200 or 250 volts, with apeak voltage range of 50 to 150 volts preferred. The energy of theauxiliary pulse may be from 0.01 or 0.05 to 1 or 2 Joules. The energy ofthe defibrillation pulse may be from 5 or 10 Joules to 30, 40 or 50Joules. An object of the instant invention is to enable the reduction ofthe size of the implantable defibrillator, which is made possible bydefibrillation pulse energy ranges as described. Thus, a further aspectof the present invention is an implantable defibrillator comprising ahousing and a power supply contained within the housing, and a controlcircuit contained within the housing and operatively associated with thepower supply. The control circuit is configured for delivering acardioversion sequence as described above. Based on the ranges above,the maximum storage capacity of the capacitor in the power supply may befrom 5.01 to 52 Joules, and is most preferably from 10 or 15 to 20Joules. Thus the housing for such a power supply preferably has a volumeless than 35 cubic centimeters (but typically at least 5 cubiccentimeters).

Without wishing to be bound to any particular theory for the preferredwaveforms described above, it appears that the auxiliary pulse, which isof a magnitude greater than pacing pulses but less than a defibrillationpulse, is sufficient to affect/substantially alter the intrinsicpatterns of recovery of excitability and thereby momentarily yieldlocalized cessation of propagation by inactivating sodium ionconductance channels via elevation of the transmembrane potential.Importantly, the tissue portions affected by the auxiliary pulse istissue in a weak field area for the primary, or defibrillation,pulse.The weak field area affected by the auxiliary pulse should be selectedto include the weakest field area of the primary pulse. In a preferredembodiment, the weak field area is generally the left lateral aspect ofthe left ventricle, extending from the apex to the base thereof.

Numerous different embodiments of the implantable system of the presentinvention can be implemented with the apparatus of FIGS. 1 and 2 and thewaveforms of FIGS. 3 and 4, depending on the specific configuration ofthe control circuitry for the use and pairing of particular electrodes.Specific examples are discussed below.

Table 1 illustrates a first embodiment of the invention. After atachyarrhythmic condition is detected and reconfirmed by algorithmsrunning in the controller 74, therapy in the form of an electrical shockof FIG. 3 is applied to the heart by discharging capacitor 78. Apreferred pairing of electrodes for this embodiment is illustrated inTable 1 below. In all tables herein, a “+” indicates that the electrodesare electrically common, and an “−>” indicating current flow (which maybe reversed).

TABLE 1 Electrode Pairings Primary Pulse B + C -> A + D

Table 2 illustrates a second embodiment of the invention. Thisembodiment introduces the use of an auxiliary pulse, with four possibleconfigurations being shown in FIG. 4. The auxiliary pulse is deliveredthrough a different set of electrodes than the primary, ordefibrillation, pulse.

TABLE 2 Electrode Selection Auxiliary Pulse Primary Pulse C -> D A -> DA -> B C -> B C -> A B -> C B -> D C -> A C -> D B -> D C -> B B -> A +D

In one embodiment of an apparatus configured according to Table 2, thecontrol circuitry is configured so that only one capacitor is employedto deliver both pulses, and that the different sets of electrodes areswitched in and out of the discharge circuit to achieve the therapeuticeffect. In this embodiment, the trailing edge of the auxiliary pulse isequal to the leading edge of the primary pulse.

In another embodiment of an apparatus configured according to Table 2,the control circuitry is configured so that the auxiliary pulse and theprimary pulse arise from separate capacitors. For example, if the designgoal is to control the time constant of the capacitor discharge waveform(time constant is the product of the resistance and the capacitance) andassuming further that the resistance to the shock (ratio of voltage tocurrent) along the auxiliary pathway is two-fold higher than along theprimary pathway, then the capacitance of the auxiliary capacitor couldbe half that of the primary shock capacitor. Further, with a twocapacitor implementation, the relative strength of the pulses can bemade independent. In this way, the minimum auxiliary shock strength canbe applied that produces the synergistic action between the auxiliaryand primary shocks, thereby minimizing the shock strength requirementsfor effective defibrillation.

Table 3 below and FIG. 5 illustrate another embodiment of the invention,where the beneficial effects are augmented by placing an additionalelectrode E; 53 on endocardial transvenous elongate lead 23 in the areaof the heart experiencing the weakest electric field when electrode C;52 is present. The weak field area in this location is in the region ofthe right ventricular conus. Specifically, the electrode E can belocated within the right atrial appendage or the right ventricularoutflow track. To accomplish this, the electrode should be located atthe most distal portion of the lead body. One configuration for pairingof electrodes in this embodiment is given in Table 3:

TABLE 3 Electrode Pairings for FIG. 5 Auxiliary Pulse Primary Pulse C ->E B -> A + D

Two embodiments of a suitable transvenous elongate electrode lead 23 areillustrated in FIG. 6, with 6 a showing a pace/sense electrode 54located at the distal tip of the lead 23, while the distal end of theprimary electrode 53 is located 10 to 15 millimeters from the top so asto minimize the shock effects on sensing from tissue very near thepace/sense electrode. Sensing of atrial activity is accomplished bymeasuring the potential difference between the pace/sense electrode 54and some indifferent electrode such as the shock coil or an electrodeaway from the heart such as electrode D 16. In the embodiment of 6 b, apair of pace/sense ring electrodes 54, 54′ are located proximal to theprimary electrode 53. The primary electrode is about 15 to 25millimeters in length, most preferably 20 millimeters in length, andpreferably about 4 to 6 French in diameter, the pair of ring electrodes(2-4 millimeters in length together, with a diameter at least equal tothat of the lead body) being positioned 10 to 20 millimeters proximal tothe primary electrode. Pacing and sensing capability on lead 23 areparticularly important when the system 10 is configured to monitorelectrical rhythm activity in both atrial and ventricular chambers.

Table 4 below, taken together with the apparatus of FIG. 3 implementingthe waveform of FIG. 4, illustrate three additional configurations ofthe present invention:

TABLE 4 Electrode Pairings Auxiliary Pulse Primary Pulse B -> C B + C ->A + D C -> D B + C -> A + D C -> D B -> C + A + D

FIG. 7 presents a flow chart schematically illustrating how theelectrodes employed to carry out the present invention can be used tomodify the therapy delivered. In FIG. 7, electrode C permits sensing ofelectrical rhythm information and furthermore, allows the implanteddevice to use that information to select therapy that is tailored tospecific rhythm characteristics. In FIG. 7 electrodes C and B areelectrically common during sensing and the combined signal is fed into asensing module for subsequent feature extraction, therapy adaptation inlight of the detected feature, and therapy delivery. For example, thetime at which the shock is delivered is determined by an algorithm thatchooses the optimum time for the defibrillation shock to produce itsmost significant electrophysiological effects. Other therapy adaptationsinclude the coupling interval between the auxiliary and primary pulses.Several features that could be used alone or in a combined, weightedfashion include mean activation interval, negative and positive slopethreshold. In the alternative, rather than electrodes C and D beingcommon, electrograms recorded between electrodes B and C and a commonindifferent electrode (electrodes A or D) could be separately fed intothe sensing module 60. The feature extraction algorithm can examinefeatures from each electrogram signal alone or in a differentialfashion. As previously, the features extracted are then used to guidetherapy adaptation and optimize therapy delivery.

Additional embodiments of the present invention are illustrated in Table5 below, taken in conjunction with the electrode placements illustratedin FIG. 5 and the waveforms presented in FIG. 13, illustrate additionalconfigurations for shocks and electrodes of the present invention.

TABLE 5 No. Figure Primary Pulse Auxiliary Pulse 1 13a B -> A + D C ->A + D 2 13a B -> D C -> A 3 13b B -> A + D C -> A + D 4 13b B -> D C ->A 5 13c B -> A + D C -> A + D 6 13c B -> D C -> A 7 13d B -> A + D C ->A + D 8 13d B -> D C -> A

In Table 5, Current flow is indicated by the direction of the arrow fromanode (+) to cathode (−). The most preferred configuration is currentlyNumber 5 in Table 5 and FIG. 13C, with a biphasic primary, ordefibrillation pulse, followed by a biphasic auxiliary pulse, with thefirst phase of the auxiliary pulse of opposite polarity from the secondphase of the primary pulse, with the primary pulse delivered between aright ventricle electrode B and two electrically common electrodes A andD; and with the auxiliary electrode delivered between the left ventricleelectrode C and two eletrically commone electrodes A and D.

In alternate embodiments of the invention, the order of the primarypulse and auxilary pulse for the embodiments set forth in Tables 2through 5 may be reversed.

Systems as described above may be implanted in a patient by conventionalsurgical techniques, or techniques readily apparent to skilled surgeonsin light of the disclosure provided herein, to provide an implanteddefibrillation or cardioversion system.

Additional features can also be added to the invention without affectingthe function of the invention and result thereof. Such additionalfeatures include, but are not limited to, saftyty features such as noisesuppression or multiple wave monitoring devices (R and T), verificationchecking to reduce false positive, precardioversion warning, programeddelayed intervention, bipolar configured sensing electrodes,intermittently activated defibrillation detector to reduce energy drain,a switching unit to minimize lines from the pulse generator, etc.

Although the system has been described above as an implantable system,it will be appreciated by those of ordinary skill in the art that theinvention could also be incorporated into an external system whichemploys catheters to position the electrodes for a short time within apatient's heart.

The present invention is explained further in the following non-limitingexamples.

EXAMPLE 1 Sub-threshold, Critically-timed,Monophasic EpicardialPre-shock Significantly Reduces Transvenous Biphasic DefibrillationThreshold in Swine

This example shows that the strength and temporal prematurety of themonophasic auxiliary shock significantly affects the strength of thedefibrillation threshold of the biphasic primary shock.

Animal model preparation. Domestic farm swine (30-35 kg) weretranquilized via an intramuscular injection of ketamine (20 mg/kg).After about 15 minutes, anesthesia was induced with an intravenous bolusinjection of sodium pentobarbital (30 mg/kg) through a 20 gauge needleplaced in a prominent ear vein. An endotracheal tube was inserted andthe cuff was inflated to provide closed circuit ventilation.Electrocardiographic monitoring leads were placed on cleaned and shavedportions of the fore limbs and hind limbs. The animal was placed indorsal recumbence and secured to the table with limb restraints. A deepsurgical plane of anesthesia was maintained with continuous intravenousinfusion of sodium pentobarbital (0.05 mg/kg/min). Skeletal muscleparalysis was induced with intravenous succinylcholine (1 mg/kg) andmaintained with a dosage of 0.25 to 0.50 mg/kg each hour. Additionalintravenous injections of sodium pentobarbital (10-20 mg) were given totitrate the anesthesia to an appropriate level. Sterile 0.9% salinesolution was infused (2-5 ml/kg/hr) through a central venous catheterplaced in an internal jugular vein. A femoral artery was surgicallyexposed and isolated through an inguinal cutdown. A 4 Frenchpolyurethane catheter was inserted and its tip was advanced into thedescending aorta. Central arterial pressure was continuously displayedon a monitor (Hewlett Packard Corp.). Anesthesia level was routinelymonitored by testing cardiac reflex response to intense pedalpressure,jaw tone and basal heart rate and pressure. Both arterial bloodelectrolytes (K₊, HCO₃ ⁻and Ca+), blood gasses pO₂, pCO₂) and pH weremeasured every 30-60 minutes. Abnormal values were corrected by addingelectrolytes to the hydration fluids and by adjusting ventilation rateand tidal volume. Esophageal temperature was continuously monitored.Heated water circulating mats were used to maintain anormothermia(36°-38° C.).

The chest was opened through a median sternotomy. A retractor wasinstalled to improve exposure of the heart and surrounding organs. Thepericardium was carefully incised along an axis connecting the base andapex of the heart. A perpendicardial cradle was fashioned to elevate theheart to a closed-chest position within the chest cavity. Throughouteach experiment, the surface of the heart was kept moist and warm byflushing its surface with normal saline and covering the chest cavitywith a sheet of plastic.

Defibrillation electrode placement. Four defibrillation electrodes wereused in this study; two for the primary shocks and two for themonophasic auxiliary shocks. Defibrillation electrodes mounted on acommercially available lead system (ENDOTAK® model 0094, CPI/GuidantCorp., St. Paul, Minn.) were introduced through a right jugularvenotomy. The distal coil electrode (4.0 cm length) was advanced underfluoroscopic guidance to the right ventricular apex. The proximal coil(6.8 cm length) was positioned with its distal tip 1 to 2 cm cephalid tothe junction of the right atrium and superior vena cava usingfluoroscopic guidance. The distal and proximal catheter electrodes wereused to deliver all the biphasic shocks.

To deliver the monophasic auxiliary shocks, an epicardial electrodeformed by concentric ellipses fashioned from platinum coated titaniumcoils 2 mm in diameter was sutured to the lateral, apical aspect of theleft ventricular free wall. This coil-patch electrode circumscribedabout 15 cm² and extended from the apex to about two-thirds the distancefrom the apex to base. The return electrode, a 6 French titanium coilelectrode, 6.8 cm in length, was positioned in the left jugular vein.

After the electrodes were inserted, margins of the incised pericardiumwere opposed by crossing the cradle tethers and applying gentletraction. The chest retractor was removed, but the chest was notsurgically closed. The chest wound was covered with an impermeableplastic drape to keep the heart warm and moist.

Test procedures. The defibrillation threshold was determined inrandomized order for each of thirteen experimental treatments in eachanimal.

Fibrillation. Ventricular fibrillation was induced with 60 Hzalternating current (50-100 mA peak to peak) applied to the pacing tipelectrode of the endocardial lead positioned in the right ventricle. Inall episodes, fibrillation was allowed to persist for at least 10seconds but not more than 12 seconds prior to delivery of thedefibrillation test shock. When the test failed to defibrillate, theheart was immediately defibrillated with a rescue shock given throughthe transvenous catheter lead system. The animal was allowed to recoverat least four minutes between each test shock.

Defibrillation waveforms. External defibrillators were used to deliverthe monophasic and biphasic truncated exponential shocks over twodifferent current pathways. The monophasic shock is referred to as the“auxiliary” pulse and the biphasic shock as the “primary” pulse herein.When delivered simultaneously, the leading edges of both pulses aretemporally coincident. When the shocks are given sequentially, theauxiliary primary coupling interval is defined as the time between thetrailing edge of the auxiliary pulse and the leading edge of the primarypulse.

All biphasic shocks were delivered by the VENTAK® external cardioverterdefibrillator(model 2815, CPI/Guidant Corp., St Paul, Minn.). Thisdevice delivers shocks having an overall fixed-tilt of 80%. Thecapacitance is 140 μF. Total waveform duration varies with shockimpedance. Phase one was always 60% of the total duration. Leading edgevoltage could be adjusted in 1-volt steps.

The monophasic shocks were delivered by a research defibrillator. Theresearch defibrillator delivers fixed-duration shocks (1-20 ms) with aneffective capacitance of 150 μF. In this study, the monophasic auxiliarypulses were always 5 ms in duration. The initiation of capacitordischarge for both shock generating devices could be externallytriggered using a low-amplitude (1-5 volts) pulse. We used acommercially-available current source (Bloom Stimulator, Bloom & Assoc.,Reading, Pa.) to generate 1 ms trigger pulses on two independent outputchannels that were used to control the relative timing between theauxiliary and primary pulses.

The polarity of the defibrillation electrodes was controlled in eachexperiment since it has been shown that defibrillation can be affectedby electrode polarity. The left ventricular electrode was alwaysconnected to the anodic terminal (positive) of the defibrillator outputcircuit, while the right ventricular defibrillation coil electrode wasalways connected to the cathodic terminal (negative).

Experimental protocol. In general, each experiment consisted of multipleepisodes of electrically-inducedventricular fibrillation that wereintentionally terminated with test shocks. by applying an establishedset of rules to the observed outcome of each defibrillation trial, shockstrengths were selected that permitted the definition of adefibrillation threshold for each experimental treatment. We used themodified Purdue technique to determine defibrillation thresholds. Inbrief, the strength of the test shock is adjusted according to theoutcome (success or failure). The first defibrillation test shock foreach treatment in the first animal was 400 V. In all subsequentexperiments, the initial test shock strength was adjusted to the meanfrom the previous animals. If the first test shock failed the next shockvoltage was increased 80 V and decreased 80 V if it succeeded. After thefirst reversal of outcome on successive trials (success to failure orfailure to success), the shock strength step was reduced to 40 V. Trialscontinued until a second outcome reversal was encountered, after whichthe strength was increased 20 V for a failure and decreased 20 V for asuccess. The lowest shock strength that defibrillated the ventricles wasdefined as the defibrillation threshold.

In this study, we investigated the influence of two variables on thedefibrillation threshold of the primary shock: 1) peak voltage of theauxiliary pulse and 2) auxiliary-primary pulse coupling interval. Theprimary pulse given alone was used as the control treatment. Threemonophasic auxiliary pulse strengths were tested: 50 V, 100 V and 150 V.Each auxiliary pulse strength was tested in combination with anauxiliary-primary pulse coupling interval. Four auxiliary-primary pulsecoupling intervals, defined as the time between the trailing edge of theauxiliary pulse and the leading edge of the primary pulse, were tested:−5 ms (simultaneous delivery), 1 ms, 20 ms and 40 ms. The combination ofthe two variables and the control yields thirteen treatments as shown inFIG. 9. The experimental treatments were tested in randomized order ineach animal.

Data acquisition. Defibrillation threshold measurements are moreaccurate and precise when shock strength measurements are made directlyacross the defibrillation electrodes. Therefore, the current and voltageduring the defibrillation pulses were measured through 4:1 and 200:1dividers by a waveform analyzer (model 6100, Data Precision, Inc.,Danvers, Mass.). The analog current and voltage signals were digitizedat 20 kHz and stored in a buffer. The digitized waveforms were displayedafter each defibrillation attempt to permit visual inspection. Customanalysis software was used to define the time and amplitude of theleading and trailing edges and to compute the shock impedance and totalenergy delivered in each pulse. Peak voltage, peak current, shockimpedance and energy delivered was recorded for each test shock.

Analysis and results. The mean and standard deviation of peak voltage,peak current, delivered energy and shock impedance for each pulse atdefibrillation threshold for each treatment were calculated for theeight animals. For the treatments utilizing an auxiliary pulse, the meantotal delivery energy values include the energy delivered in themonophasic pulse. The mean peak current and peak voltage values alwaysreflect the strength of the biphasic primary pulse.

Repeated measures analysis of variance with the Student Newman-Keul'stest was used to compare peak voltage, peak current, delivered energyand shock impedance among the treatments. Differences among the meanswere considered significant when P<0.05. All reported values are mean±SD unless noted otherwise.

The mean energy delivered at defibrillation threshold for each of theexperimental treatments is presented in FIG. 9. The mean defibrillationthreshold for the control treatment was 24±10.4 J. The defibrillationthresholds were significantly lower (˜50%) when a monophasic auxiliarypulse was delivered simultaneously with the biphasic primary pulse. Themean energy delivered in the 50, 100 and 150 V monophasic pulses was0.09 J, 0.38 J and 0.87 J, respectively. However, there was nosignificant differences among the simultaneous treatments. Similarly,the defibrillation thresholds for the treatments with a 1 ms auxiliary-primary pulse coupling interval were significantly lower than control,and unlike the simultaneous treatments, there was a trend suggestingthat the strength of the monophasic pulse affected the amount ofdefibrillation threshold reduction.

Peak voltage requirements at defibrillation threshold followed trendsvery similar to the trends for energy delivered. FIG. 10 shows mean peakvoltage of the primary pulse at defibrillation threshold with andwithout the auxiliary pulse. When the auxiliary and primary pulses wereapplied simultaneously, the peak voltage defibrillation threshold wasreduced about 25%. For auxiliary-primary coupling intervals of 20 ms and40 ms, the defibrillation thresholds were not different than control forauxiliary shocks of 50 V and 100 V. However, the defibrillationthresholdfor the 150 V auxiliary shock with a 20 ms auxiliary-primary couplinginterval was significantly lower than the control treatment (P<0.05).

EXAMPLE 2 Single Capacitor Implementation of Dual Shock DefibrillationMethod in Closed-Chest Dogs

This example demonstrates the feasibility of the dual shockdefibrillation therapy demonstrated in Example 1 above with a singlecapacitor implementation, and with a transvenous lead system.

Animal model preparation. A total of six animals were studied. Methodsof preparation were essentially equivalent for each animal. Mixed-breedcanines (26-36 kg) were tranquilized via an intramuscular injection ofketamine (10 mg/kg), if necessary. After about 15 minutes, anesthesiawas induced with an intravenous bolus injection of sodium pentobarbital(30 mg/kg) through a catheter placed in a cephalic vein. An endotrachealtube was inserted and the cuff was inflated to provide closed circuitventilation. Electrocardiographic monitoring leads were placed on thecleaned and shaved portions of the fore limbs and hind limbs. The animalwas placed in dorsal recumbence and secured to the table with limbrestraints. A deep surgical plane of anesthesia was maintained withcontinuous intravenous infusion of sodium pentobarbital (0.05mg/kg/min). Skeletal muscle paralysis was induced with intravenoussuccinylcholine(1 mg/kg) and maintained with a dosage of 0.25 to 0.50mg/kg each hour. Additional intravenous injections of sodiumpentobarbital (10-20 mg) were given to titrate the anesthesia to anappropriate level prior to performing any surgical procedures. Sterile0.9% saline solution was infused (2-5 ml/kg/hr) through a central venouscatheter placed in an internal jugular vein. A femoral artery wassurgically exposed and isolated. A 4 French polyurethane catheter wasinserted and its tip was advanced into the descending aorta. Centralarterial pressure was continuously displayed on a monitor (HewlettPackard Corp.). Anesthesia level was routinely monitored by testingcardiac reflex response to intense pedal pressure, jaw tone and basalheart rate and blood pressure. Both arterial blood electrolytes, bloodgasses, as well as pH were measured every 30-60 minutes. Abnormal valueswere corrected by adding electrolytes to the hydration fluids and byadjusting ventilation rate and tidal volume. Esophageal temperature wascontinuously monitored. Heated water-circulating mats were used tomaintain a normothermia (36°-38° C.).

The chest was opened through a median stemotomy. A retractor wasinstalled to improve exposure of the heart and surrounding organs. Thepericardium was carefully incised along an axis connecting the base andapex of the heart. A pericardial cradle was fashioned to elevate theheart to a closed-chest position within the chest cavity. When the chestwas open during the initial stages of the study, the surface of theheart was kept moist and warm by flushing its surface with normal salineand covering the chest cavity with a sheet of plastic.

Defibrillation electrode placement. Four defibrillation electrodes wereused in this study; two for the primary shocks and two for themonophasic auxiliary shocks (see FIG. 11). Defibrillation electrodesmounted on a commercially available lead system (ENDOTAK® model 0094,CPI/Guidant Corp., St. Paul, Minn.) were introduced through a rightjugular venotomy. The distal coil electrode (4.0 cm length) was advancedunder fluoroscopic guidance to the right ventricular apex. The proximalcoil (6.8 cm length) was positioned with its distal tip 1 to 2 cmcephalid to the junction of the right atrium and superior vena cavausing fluoroscopic guidance. The distal and proximal catheter electrodeswere used to deliver all the biphasic shocks.

We elected to simulate a transvenous introduction of the leftventricular electrode used to deliver the monophasic auxiliary shocks.The approach was taken because we wanted to control the position of theleft ventricular electrode. Closed chest introduction and positioning ofthe left ventricular electrode using fluoroscopic guidance alone is nottrivial. Improper positions could have severely impacted the results ofthis study. Therefore, efforts were made to simulate a closed-chestmodel. To accomplish this goal, the left ventricular coil electrode (3French, 3 cm length, tri-filar platinum coated titanium) was insertedinto the posterior cardiac vein. In addition, the chest was closed andevacuated after the left ventricular electrode was positioned. Thisprocedure assured that the volume conductor characteristics of a closedchest were present at the time that defibrillation trials wereconducted. The 3 French coil electrode was inserted into the posteriorcardiac vein by elevating the apex of the heart to expose thepostero-lateral left ventricle. A short segment of an 18 gauge catheterwas partially inserted so that about 1 cm was outside the vein. Backflow of venous blood confirmed proper location. The specially designedtip of the defibrillation coil was allowed to engage the catheter whichacted as a micro-introducing sheath. Both the introducing catheter anddefibrillation electrode were carefully advanced into the vein andsecured with a single stitch. this technique was successfully used toposition the left ventricular defibrillation electrode within theposterior cardiac vein in all of the six animals.

The return electrode for the monophasic auxiliary shocks, a 6 Frenchtitanium coil electrode, 6.8 cm in length, was positioned in the leftjugular vein. See FIG. 11.

After the electrodes were inserted, margins of the incised pericardiumwere opposed by crossing the cradle tethers and applying gentletraction. The chest retractor was removed and the chest was surgicallyclosed in three layers. A chest tube was inserted and continuous suctionwas applied to evacuate the thoracic cavity.

Test procedures. The defibrillation threshold was determined inrandomized order for each of seven experimental treatments in eachanimal.

Fibrillation. Ventricular fibrillation was induced with 60 Hzalternating current (50-100 mA peak to peak) applied to the pacing tipelectrode of the endocardial lead positioned in the right ventricle. Inall episodes, fibrillation was allowed to persist for at least 10seconds but not more than 12 seconds prior to delivery of thedefibrillation test shock. When the test failed to defibrillate, theheart was immediately defibrillated with a rescue shock given throughthe transvenous catheter system. The animal was allowed to recover atleast four minutes between each test shock.

Defibrillation waveforms. External defibrillators were used to deliverthe monophasic and biphasic truncated exponential shocks over twodifferent current pathways. The monophasic shock is referred to as the“auxiliary” pulse and the biphasic shock as the “primary” pulse herein.

Three pulsing schema were tested in this study and are shown in FIG. 12.Unidirectional shocks served as control treatments. Bidirectional andsequential shocks served as the test treatments. Unidirectional shockswere given using the conventional transvenous shock vector (RV−>SVC).Bidirectional shocks were applied to electrodes in the shock vectorRV+LV−>SVC. Sequential shocks were given in a manner similar to thatdescribed in the previous chapter. However, in this study theauxiliary-primary coupling interval (defined as the time between thetrailing edge of the auxiliary pulse and the leading edge of the primarypulse) tested were 1 ms, 5 ms, 10 ms and 20 ms.

For all sequential shock treatments a single capacitor waveform wasemulated. Thus, the trailing edge of the auxiliary pulse was set equal(±10 V) to the leading edge of the primary pulse.

Biphasic primary shocks were delivered by the VENTAK® externalcardioverter defibrillator as described in Example 1 above or by aresearch defibrillator. The research defibrillator was programmed toemulate a single capacitor truncated exponential waveform. The firstphase duration was 4 ms and the second phase duration was 3 ms. Thetrailing edge of phase one was equal (±10 V) to the leading edge voltageof phase two.

All of the monophasic shocks were delivered by a research defibrillator.The research defibrillator delivers fixed-duration shocks (1-20 ms) withan effective capacitance of 150 μF. In this study, the monophasicauxiliary pulses were always 5 ms in duration. The initiation ofcapacitor discharge for both shock generating devices could beexternally triggered using a low-amplitude (1-5 volts) pulse. We used acommercially-available current source (Bloom Stimulator, Bloom & Assoc.,Reading, Pa.) to generate 1 ms trigger pulses on two independent outputchannels that were used to control the relative timing between theauxiliary and primary pulses.

The polarity of the defibrillation electrodes was controlled in eachexperiment since it has been shown that defibrillation can be affectedby electrode polarity. The left ventricular electrode was alwaysconnected to the anodic terminal (positive) of the defibrillator outputcircuit, while the right ventricular defibrillation coil electrode wasalways connected to the cathodic terminal (negative). When bidirectionalshocks were given the left ventricular electrode was connected alongwith the right ventricular electrode to the cathodic terminal of theexternal defibrillator.

Experimental protocol. In general, each experiment was carried out asdescribed in Example 1 above. The lowest shock strength thatdefibrillated the ventricles was defined as the defibrillationthreshold.

Data acquisition. Data acquisition was carried out in essentially thesame manner as described in Example 1 above. Analysis and results. Dataanalysis was carried out in essentially the same manner as described inExample 1 above. As shown with reference to FIG. 12 delivered energyrequirements at the defibrillation threshold were significantly lowerfor the dual shock treatments 4, 5, 6 and 7 (P<0.05). Differences amongthe mean energy delivered at the defibrillation threshold forunidirectional shocks (treatments 1 and 3) and bidirectional shocks(treatment 2) were not statistically significant. Additionally, none ofthe differences among the mean energy delivered at defibrillationthreshold for the sequential shocks (treatments 4, 5, 6 and 7) werestatistically significant, although there was a strong trend suggestingthat the sequential shocks having a 20 ms coupling interval requiredmore energy for defibrillation than sequential shocks having a 1 mscoupling interval (15.4±7.2J vs. 10.2±4.1J, P=0.076).

EXAMPLE 3 Effect of Varying Preshock and Postshock Tilt on Efficacy ofSequential Waveform Defibrillation Incorporating an LV Electrode

In this example, sequential waveform optimization was tested in tenswine using a four-electrode configuration incorporating a leftventricular electrode (LVA). Nine left ventricle (LV) preshock/rightventricle (RV) postshock waveforms were tested, with the tilts of thepre-and postshocks being varied across a large range (20-60%). TRIAD™apparatus (available from Guidant Corporation Cardiac Pacemakers (CPI),4100 Hamline Avenue North, St. Paul, Minn. 55112-5798) and an RVpreshock/LV postshock waveform were used as controls.

Methods. The swine were pre-anesthetizedwith a 2.5 ml IM injection ofTelazol, ketamine and xylazine mixture (50 mg/ml tiletamine, 50 mg/mlketamine, 50 mg/ml xylazine), then were anesthetized with sodiumpentothal (50 mg/kg) injected through a cannulated ear vein. They werethen intubated with a cuffed endotracheal tube and placed on aventilator, where then were maintained on an oxygen/isoflurane mixture.

Under fluoroscopy, an ENDOTAK® lead (available from Guidant CorporationCardiac Pacemakers (CPI))) was inserted via a jugular venotomy into theright ventricle. A subclavicular, subcutaneous pocket was made on theleft thorax for insertion of a MINI II “active can” emulator (can). Anarterial line was placed in the carotid artory to monitor bloodpressure.

A 3 cm DBS electrode was used as the LVA lead in this study. To implantthe LVA lead, first a median sternotomy was performed. The exposedpericardium was then incised and the electrode was sutured to theepicardium in a position approximating the path of the lateral coronaryvein. The pericardium was then sutured closed. The LVA lead was broughtout through the chest wall at the fifth intercostal space. A chest tubewas added for drainage. The sternotomy was then closed and the chestevacuated. Fifteen ohms of external resistance was connected to the LVAlead to simulate a prototype LVA lead. The RV vector for preshocks andpostshocks was RV−> superior vena cava (SVC)+can. The LV vector forpreshocks and postshocks was LV−>SVC+can. The protocol had eleven testconfigurations:

1. TRIAD (RV−>SVC+can (control))

2. LV preshock,20% tilt preshock/20% tilt postshock

3. LV preshock, 20% tilt preshock/40% tilt postshock

4. LV preshock, 20% tilt preshock/60% tilt postshock

5. LV preshock, 40% tilt preshock/20% tilt postshock

6. LV preshock, 40% tilt preshock/40% tilt postshock

7. LV preshock, 40% tilt preshock/60% tilt postshock

8. LV preshock, 60% tilt preshock/20% tilt postshock

9. LV preshock, 60% tilt preshock/40% tilt postshock

10. LV preshock,60% tilt preshock/60% tilt postshock

11. RV preshock, 5 ms fixed duration preshock/40% tilt postshock(control). The LV preshock test waveforms (numbers 2-10 above)corresponded to the waveform of FIG. 13c number 5 and Table 5 number 5,and were consistently a fixed tilt biphasic, 60:40 duration ratio,truncated exponential preshock, followed by a 5 ms delay, and then afixed tilt, 60:40 duration ratio, biphasic, truncated exponentialpostshock. The RV preshock waveform (11) was a 5 ms fixed durationmonophasic preshock followed by a 5 ms delay and a 40% fixed tilt, 60:40biphasic postshock.

Simulated capacitance was 225 ohms for all sequential testconfigurations. Waveforms were delivered using an AWAG arbitrarywaveform generator. Voltage, current and energy data were collected withan automated data collection system.

Fibrillation was induced by two 9 volt batteries placed in series acrossthe shock coils. Fibrillation was confirmed by disorganization of thesurface ECG and loss of blood pressure. Fibrillation was allowed to runten seconds before a test shock was attempted. In the event of afailure, the animal was rescued using a 2815 ECD. Leading edge currentof the preshock was increased ten percent after failures, decreased tenpercent after successes. In either instance, animals were allowed torecover two minutes between fibrillation induction attempts. The up-downprocedure was continued until three reversals were observed.

TABLE 6 Preshock voltage, stored and total delivered energies shown forall configurations. Voltage of First Total Delivered Configuration PulseStored Energy Energy 1 474 ± 20# 16.0 ± 1.4# 15.2 ± 1.4# 2 321 ± 12*11.7 ± 0.9*  7.3 ± 0.6* 3 317 ± 13* 11.5 ± 0.9*  9.5 ± 0.8* 4 299 ± 12*10.2 ± 0.8* 10.5 ± 0.9* 5 354 ± 23* 14.6 ± 2.1  11.3 ± 1.8* 6 300 ± 18*10.4 ± 1.4*  9.0 ± 1.2* 7 286 ± 7*   9.2 ± 0.4*  9.0 ± 0.5* 8 442 ± 26#22.7 ± 2.6# 19.0 ± 2.3# 9 351 ± 19* 14.2 ± 1.7* 12.8 ± 1.7  10  380 ±27*# 17.0 ± 2.4*#  16.6 ± 2.6*# 11 311 ± 11* 11.0 ± 0.8*  9.1 ± 0.7*Values shown as mean ± SEM. *indicates statistically significant versuscontrol group 1. #indicates statistically significant versus controlgroup 11.

Waveforms with lower first shock tilts performed better from a deliveredenergy not from a voltage and stored energy standpoint. LV preshocks didnot erform RV preshocks (see number 11 above). The best overall waveformwas the 40/40 LV preshock waveform (number 6 above), which hadsignificantly lowered current, voltage and energy as compared to a TRIADwaveform (number 1 above), while still having a low stored energyrequirement.

EXAMPLE 4 Effect of Varying Preshock and Postshock Tilt on RV PreshockDual Waveform Defibrillation

Sequential waveform optimization was tested in ten swine using afour-electrode configuration incorporating a left ventricular electrode(LVA). Seven RV preshock/LV postshock waveforms of varyingpreshock/postshock tilt were tested. Various combination ofpreshock/postshock polarities, monophasic/biphasic and biphasic/biphasicpreshock/postshock treatments were also tested. A standard TRIADconfiguration and an LV preshock/RV postshock waveform were used ascontrol.

Methods. This experiment was carried out in essentially the same manneras in the example immediately above. Again, the RV vector for preshocksand postshocks was RV−>SVC+can. The LV vector for preshocks andpostshocks was LV−>SVC+can. The protocol had nine test configurations:

1. TRIAD (RV−>SVC+can (control)

2. RV biphasic (bi) preshock, 40% tilt preshock/20% tilt postshockpositive positive;

3. RV bi preshock, 40% tilt preshock 40% tilt postshock positivepositive;

4. RV bi preshock, 60% tilt preshock/20% tilt postshock positivepositive;

5. RV bi preshock, 60% tilt preshock/40% tilt postshock positivepositive;

6. RV bi preshock, 40% tilt preshock/40% tilt postshock positivenegative (the first phase of the postshock was in opposite polarity tothe first phase of the preshock);

7. RV monophasic (mono) preshock, 40% tilt preshock/40% tilt postshockpositive negative;

8. RV mono preshock, 40% tilt preshock/40% tilt postshock positivepositive;

9. LV bi preshock, 40% tilt preshock/40% tilt postshock positivepositive. Positive indicates a polarity of RV negative−>SVC positive+canpositive.

Waveforms 2-5 were designed to test the preshock/postshock tiltrelationship of RV preshock waveforms. Preshock tilts of 40% and 60% andpostshock tilts of 20% and 40% were used. Waveforms 6, 7, and 8, incombination with waveform 3, were designed to study the effect of usinga reverse polarity postshock and of using a monophasic or biphasicpreshock. Waveform 9, an LV preshock waveform found to be efficacious inthe immediately preceeding example, was included as an additionalcontrol.

Results. The results are summarized in Table 7 below.

TABLE 7 Preshock voltage, stored and total delivered energies shown forall configurations. Voltage of First Total Delivered Configuration PulseStored Energy Energy 1 512 ± 33# 19.1 ± 2.4# 18.5 ± 2.4# 2  354 ± 21*#14.5 ± 1.6* 11.1 ± 1.2* 3 323 ± 18* 12.1 ± 1.3* 10.4 ± 1.1* 4  348 ±18*# 14.0 ± 1.4*  12.5 ± 1.3*# 5  360 ± 17*# 14.9 ± 1.4*  14 ± 1.3*# 6311 ± 16* 11.1 ± 1.1*  9.6 ± 1.0* 7 298 ± 16* 10.3 ± 1.1*  8.6 ± 0.9* 8 340 ± 17*{circumflex over ( )}  13.3 ± 1.4*{circumflex over ( )} 11.5 ±1.2* 9 297 ± 14* 10.1 ± 0.9*  8.9 ± 0.8* Values shown as mean ± SEM.*indicates statistically significant versus control group 1. #indicatesstatistically significant versus group 9. {circumflex over ( )}indicatessignificantly different from configuration 7.

All dual shock waveforms performed significantly better than the TRIADgroup (1) for delivered energy, voltage and stored energy. 40% tilts forpre- and postshock were efficacious and a good compromise for voltage,current, and energy requirements. Using the RV for the preshock is aseffective as using the LV for the same combination of pre and postshocktilt (configurations 3 vs. 9). Biphasic/monophasic preshock did notmatter (configuration 2, 3 vs. 7,8). Relative polarity of the pre andpostshock matters for the monophasic preshock (configurations 7 vs. 8)but not for biphasic (configurations 3 vs. 6). configuration 6 iscurrently most preferred.

The foregoing is illustrative of the present invention, and is not to beconstrued as limiting thereof. The invention is defined by the followingclaims, with equivalents of the claims to be included therein.

That which is claimed is:
 1. An implantable system for the delivery of acardioversion pulse to a patient's heart, comprising: a plurality ofprimary stimulation electrodes configured for sensing cardiac signalsand delivering a cardioversion pulse to said heart; a first one of saidprimary stimulation electrodes configured for positioning through thecoronary sinus ostium and within a vein on the surface of the leftventricle of said heart; a sensing electrode positioned within saidheart; a power supply; and a control circuit operatively associated withsaid power supply and said primary stimulation electrodes, said controlcircuit configured for delivering a cardioversion pulse through saidprimary stimulation electrodes, wherein said control circuit includes acapacitor.
 2. A system according to claim 1, wherein said primaryelectrodes are configured for delivering a cardioversion pulse to theventricles of said heart.
 3. A system according to claim 1, wherein afirst one of said primary electrodes is configured for positioningthrough the coronary sinus and within a vein on the antero lateralsurface of the left ventricle of said heart.
 4. A system according toclaim 1, wherein a first one of said primary electrodes is configuredfor positioning through the coronary sinus and in a vein on thepostero-lateral surface of the left ventricle of said heart.
 5. A systemaccording to claim 1, wherein a first one of said primary electrodes isconfigured for positioning through the coronary sinus and in either theapical third of the posterior cardiac vein or the apical half of thegreat cardiac vein.
 6. A system according to claim 1, wherein said powersupply includes a 20 to 400 microfarad capacitor.
 7. A system accordingto claim 1, wherein each one of said primary electrodes is carried by atransvenous lead.
 8. A system according to claim 1, wherein saidplurality of primary electrodes are carried by a common transvenouslead.
 9. An implantable system for the delivery of a cardioversion pulseto a patient's heart, comprising: a plurality of primary electrodesconfigured for delivering a cardioversion pulse to said heart; a firstone of said primary electrodes configured for positioning through thecoronary sinus ostium and within a vein on the surface of the leftventricle of said heart; a sensing electrode positioned within saidheart; a power supply; and a control circuit operatively associated withsaid power supply and said primary electrodes, said control circuitconfigured for delivering a cardioversion pulse through said primaryelectrodes, wherein a first one of said primary electrodes is configuredfor positioning through the coronary sinus and within a vein on theantero-lateral surface of the left ventricle of said heart.
 10. A systemaccording to claim 9, wherein said primary electrodes are configured fordelivering a cardioversion pulse to the ventricles of said heart.
 11. Asystem according to claim 9, wherein a first one of said primaryelectrodes is configured for positioning through the coronary sinus andin either the apical third of the posterior cardiac vein or the apicalhalf of the great cardiac vein.
 12. A system according to claim 9,wherein said power supply includes a capacitor.
 13. A system accordingto claim 9, wherein said power supply includes a 20 to 400 microfaradcapacitor.
 14. A system according to claim 9, wherein each one of saidprimary electrodes is carried by a transvenous lead.
 15. A systemaccording to claim 9, wherein said plurality of primary electrodes arecarried by a common transvenous lead.
 16. An implantable system for thedelivery of a cardioversion pulse to a patient's heart, comprising: aplurality of primary electrodes configured for delivering acardioversion pulse to said heart; a first one of said primaryelectrodes configured for positioning through the coronary sinus ostiumand within a vein on the surface of the left ventricle of said heart; asensing electrode positioned within said heart; a power supply; and acontrol circuit operatively associated with said power supply and saidprimary electrodes, said control circuit configured for delivering acardioversion pulse through said primary electrodes, wherein a first oneof said primary electrodes is configured for positioning through thecoronary sinus and in a vein on the postero-lateral surface of the leftventricle of said heart.
 17. A system according to claim 16, whereinsaid primary electrodes are configured for delivering a cardioversionpulse to the ventricles of said heart.
 18. A system according to claim16, wherein a first one of said primary electrodes is configured forpositioning through the coronary sinus and in either the apical third ofthe posterior cardiac vein or the apical half of the great cardiac vein.19. A system according to claim 16, wherein said power supply includes acapacitor.
 20. A system according to claim 16, wherein said power supplyincludes a 20 to 400 microfarad capacitor.
 21. A system according toclaim 16, wherein each one of said primary electrodes is carried by atransvenous lead.
 22. A system according to claim 16, wherein saidplurality of primary electrodes are carried by a common transvenouslead.